This is a multi-disciplinary project aimed at studying the etiology and pathogenesis of Hyaline Membrane Disease to try to better understand some of the mechanisms through which therapy is effectual, and to look at long-term outcome in infants who have had the disease. The specific aims of this proposal are: 1) To better understand the normal development and regulation of the surfactant system of the lung by studying mechanisms regulating Type II cell maturation, surfactant production, production sites of its various components, and modulation of its secretion. 2) To determine the functional integrity of the surfactant system during the various phases of the course of hyaline membrane disease. 3) To determine if the pulmonary ischemia which preceeds the development of HMD may be of reflex origin. 4) To determine the physiological and pathological consequences of a patent ductus arteriosus on the acute and convalescent course of HMD and on respiratory failure in small premature infants. 5) To devise improved techniques, using statistical modeling and computer analysis, of diagnosis, anticipation of events, regulation of specific therapy and monitoring of short and long-term outcome in infants with HMD. 6) To develop better methods of evaluating the effects of HMD and its changing modes of therapy on the long-term outcome of infants who have been treated in our NICU over the past fifteen years.